Improvement of adjunctive berberine treatment on negative symptoms in patients with schizophrenia.

The upregulation of immune and inflammatory response may play a role in the negative symptoms of schizophrenia. Berberine is an effective drug with anti-inflammatory property, and may be beneficial for the treatment of negative symptoms. The aim of this study is to test this hypothesis through a randomized, double-blind, placebo-controlled, clinical trial. Eligible patients with schizophrenia were randomized to receive placebo or berberine (900 mg/day) for 8 weeks as adjunctive treatment to single atypical antipsychotic drug. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate clinical symptoms at three time points (baseline, 4th and 8th week). Blood samples were collected at the above three time points to determine the concentrations of inflammatory markers including interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). 59 patients with intention-to-treat were analyzed, 32 in the berberine group and 27 in the placebo group. From the baseline to the 8th week, berberine treatment significantly improved the negative symptom subscale of PANSS (F = 18.981; p < 0.001). From the baseline to the 8th week, the plasma CRP concentration decreased in the berberine group, while increased in the placebo group (F = 5.373; p = 0.024). Furthermore, in the berberine group, the change of CRP concentration was significantly positively correlated with the change of PANSS negative symptom subscale within 8 weeks (r = 0.56; p = 0.002). There was no significant difference in adverse events between the two groups (p's > 0.05). Our study suggests that berberine treatment is well tolerated in patients with schizophrenia. Berberine may improve negative symptoms through anti-inflammatory effect.Trial registration: Clinicaltrials.gov identifier: NCT03548155.

A Pilot Remote Drama Therapy Program Using the Co-active Therapeutic Theater Model in People with Serious Mental Illness.

The impact of drama therapy on mental health recovery remains poorly understood. We examined the effects of a pilot remote drama therapy program for community members living with serious mental illness. The entire intervention was delivered remotely. Participants with serious mental illness completed a 12-week drama therapy program which included an online performance open to the public. Four quantitative scales were administered pre- and post-program. A focus group was conducted 1 week after the performance. Six participants completed the program and crafted a public performance themed around hope. No significant differences were identified in the quantitative measures. Five themes were identified in the post-performance focus group. Drama therapy presents an opportunity for individuals with serious mental illness to process and share their journeys with their diagnoses and re-create a healthy sense of self with increased community awareness.

Association of Aripiprazole With Reduced Hippocampal Atrophy During Maintenance Treatment of First-Episode Schizophrenia.

PURPOSE/BACKGROUND: Hippocampal volume loss in early schizophrenia has been linked with markers of inflammation and oxidative stress, and with less response of negative symptoms. Aripiprazole has been reported to preserve hippocampal volume and to reduce inflammation. METHODS/PROCEDURES: Study 1 was a 12-month multicenter randomized placebo-controlled trial of citalopram added to clinician-determined second-generation antipsychotic medication in 95 patients with first-episode schizophrenia (FES), 19 of whom received aripiprazole. We compared participants taking aripiprazole with those on other antipsychotics to determine whether those on aripiprazole had less hippocampal volume loss. We also examined peripheral biomarker data from medication-naive patients with schizophrenia receiving 8 weeks of antipsychotic treatment (n = 24) to see whether markers of inflammation and oxidative stress that previously predicted hippocampal volume differed between aripiprazole (n = 9) and other antipsychotics (study 2). FINDINGS/RESULTS: Aripiprazole was associated with a mean increase in hippocampal volume of 0.35% (SD, 0.80%) compared with a 0.53% decrease (SD, 1.2%) with other antipsychotics during the first year of maintenance treatment in patients with FES. This difference was significant after adjusting for age, sex, citalopram treatment, and baseline Brief Psychiatric Rating Scale score (B = 0.0079, P = 0.03). Aripiprazole was also associated with reduced concentrations of the inflammatory cytokines interleukin-8 and tumor necrosis factor (P < 0.01) during the first 8 weeks of treatment in medication-naive patients with FES. IMPLICATIONS/CONCLUSIONS: These results suggest that aripiprazole may protect against hippocampal atrophy via an anti-inflammatory mechanism, but these results require replication in larger, randomized trials, and the clinical relevance of hippocampal volume loss is not established.

Methamphetamine-associated psychosis: Clinical presentation, biological basis, and treatment options.

INTRODUCTION: Methamphetamine associated psychosis (MAP) represents a mental disorder induced by chronic methamphetamine use in a subset of users. The prevalence of the disorder has increased in several countries in Europe and Asia where methamphetamine use has increased. MAP remains difficult to distinguish from primary psychiatric disorders, especially schizophrenia, creating complications in prescribing treatment plans to patients. DESIGN: This narrative review sought to summarize difficulties related to MAP diagnosis and highlight the need for a better treatment model. Current best practices are described and potential novel therapies and future research suggested. RESULTS: Results suggest that clear biological and clinical differences appear between patients presenting with MAP and schizophrenia and that there may exist distinct subgroups within MAP itself. MAP-specific treatment studies have been few and have focused on the use of antipsychotic medication. Antipsychotic treatment has been shown to alleviate the psychotic symptoms of MAP but produce debilitating adverse effects and fail to adequately address methamphetamine use in patients. CONCLUSIONS: Continued identification of subgroups within the heterogenous MAP population may lead to better diagnosis, treatment, and outcomes for patients. Psychosocial therapies should be explored in addressing the cooccurring substance use and psychosis in the treatment of MAP.

Mixed methods to explore factors associated with the decline of patients in the methadone maintenance treatment program in Shanghai, China.

BACKGROUND: This study was to characterize the Methadone Maintenance Treatment (MMT) in Shanghai, China, and to explore factors associated with the decline of patients in MMT during 2005-2016. METHODS: Both qualitative and quantitative methods were used in this study. Based on the data from Shanghai Centers for Disease Control (CDC), we described the changes in the number of patients who received MMT, and new enrollment each year from 2005 to 2016. Focus groups were conducted with 22 patients, and in-depth interviews were conducted with 9 service providers. RESULTS: Quantitative data demonstrate that the number of new enrollment began to decline in 2009, and the number of patients receiving MMT began to decline in 2012. The main reasons for dropout include (1) discontinuing medication due to unknown reasons (25%), (2) criminal activities other than drug-related crimes (20%), (3) relapse to heroin use (16%), and (4) physical disease (10%). Qualitative assessment results indicate that the major reasons for the decline of patients in MMT are as follows: (1) the increase of Amphetamine-type stimulants (ATS) use in recent years, (2) limited knowledge about MMT in both patients and MMT staff, (3) complicated enrollment criteria, and (4) discrimination against drug use. CONCLUSION: Various reasons to explain the decline of patients in MMT in Shanghai, China, were identified. Government agencies, service providers, and other stakeholders need to work together and overcome identified barriers to support MMT programs in China.

No Effect of Adjunctive Minocycline Treatment on Body Metabolism in Patients With Schizophrenia.

PURPOSE/BACKGROUND: This study examined the effect of adjunctive minocycline on body metabolism in risperidone-treated patients with schizophrenia. METHODS/PROCEDURES: Each subject had a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia and had been on stable dose of risperidone for at least 4 weeks. In a 16-week randomized, double-blind, placebo-controlled study, subjects received either minocycline (200 mg/d) or placebo. Various metabolic parameters, including weight, waist circumference, fasting insulin, glucose, and lipids, were measured at baseline and week 16. FINDINGS/RESULTS: A total of 63 subjects with schizophrenia were enrolled in the study. Fifty-five patients completed week-16 assessments (27 in the minocycline group, 28 in the placebo group). There were no significant differences between the 2 groups in week 16 changes for body weight, body mass index, waist circumference, fasting insulin, glucose, and lipids (P's > 0.300). IMPLICATIONS/CONCLUSIONS: In the present study, adjunctive treatment of minocycline did not seem to improve body metabolism in patients with schizophrenia receiving risperidone. The implications for future studies were discussed.

Impaired cue identification and intention retrieval underlie prospective memory deficits in patients with first-episode schizophrenia.

OBJECTIVE: Schizophrenia is associated with impairment in prospective memory, the ability to remember to carry out an intended action in the future. It has been established that cue identification (detection of the cue event signaling that an intended action should be performed) and intention retrieval (retrieval of an intention from long-term memory following the recognition of a prospective cue) are two important processes underlying prospective memory. The purpose of this study was to examine prospective memory deficit and underlying cognitive processes in patients with first-episode schizophrenia. METHODS: This study examined cue identification and intention retrieval components of event-based prospective memory using a dual-task paradigm in 30 patients with first-episode schizophrenia and 30 healthy controls. All participants were also administered a set of tests assessing working memory and retrospective memory. RESULTS: Both cue identification and intention retrieval were impaired in patients with first-episode schizophrenia compared with healthy controls ( ps < 0.05), with a large effect size for cue identification (Cohen's d = 0.98) and a medium effect size for intention retrieval (Cohen's d = 0.62). After controlling for working memory and retrospective memory, the difference in cue identification between patients and healthy controls remained significant. However, the difference in intention retrieval between the two groups was no longer significant. In addition, there was a significant inverse relationship between cue identification and negative symptoms ( r = -0.446, p = 0.013) in the patient group. CONCLUSION: These findings suggest that both cue identification and intention retrieval in event-based prospective memory are impaired in patients with first-episode schizophrenia. Cue identification and intention retrieval could be potentially used as biomarkers for early detection and treatment prognosis of schizophrenia. In addition, addressing cue identification deficit through cognitive enhancement training may potentially improve negative symptoms as well.

Altered Neural Correlates of Emotion Associated Pain Processing in Persistent Somatoform Pain Disorder: An fMRI Study.

Patients with persistent somatoform pain disorder (PSPD) suffer from long-term pain and emotional conflicts. Recently, accumulating evidence indicated that emotion has a significant role in pain perception of somatoform pain disorder. To further understand the association between emotion and pain-related brain activities, functional activities of patients with PSPD fulfilling ICD-10 criteria and healthy controls were assessed using functional magnetic resonance imaging technology, while participants viewed a series of positive, neutral, or negative pictures with or without pinprick pain stimulation. Results showed that patients with PSPD had altered brain activities in the parietal gyrus, temporal gyrus, posterior cingulate cortex, prefrontal cortex, and parahippocampus in response to pinprick pain stimuli during different emotions compared with the healthy control group. Moreover, patients with PSPD consistently showed hyperactivities in the prefrontal, the fusiform gyrus and the insula in response to negative stimuli under pinprick pain vs. non-pain condition. The current findings provide some insights into the underlying relationship between emotion and pain-related brain activity in patients with PSPD, which is of both theoretical and clinical importance.

Fat-mass and obesity-associated gene polymorphisms and weight gain after risperidone treatment in first episode schizophrenia.

BACKGROUND: Obesity induced by antipsychotics severely increases the risk of many diseases and significantly reduces quality of life. Genome Wide Association Studies has identified fat-mass and obesity-associated (FTO) gene associated with obesity. The relationship between the FTO gene and drug-induced obesity is unclear. METHOD: Two hundred and fifty drug naïve, Chinese Han patients with first-episode schizophrenia were enrolled in the study, and genotyped for four single nucleotide polymorphisms (SNPs rs9939609, rs8050136, rs1421085 and rs9930506) by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Body weight and body mass index (BMI) were measured at baseline and six months after risperidone treatment. RESULTS: At baseline, body weight and BMI of TT homozygotes were lower than those of A allele carriers in rs9939609; body weight of AA homozygotes was higher than those of G allele carriers in rs9930506 (p's < 0.05). After 6 months of risperidone treatment, body weight and BMI of TT homozygotes were lower than those of A allele carriers in rs9939609 (p's <0.01); body weight and BMI of CC homozygotes were lower than those of A allele carriers in rs8050136 (p's < 0.05); body weight of AA homozygotes was higher than those of G allele carriers in rs9930506 (p's < 0.05). After controlling for age, gender, age of illness onset, disease duration, weight at baseline and education, weight gain of TT homozygotes at 6 months remained to be lower than those of A allele carriers in rs9939609 (p < 0.01); weight gain of CC homozygotes at 6 months was lower than those of A allele carriers in rs8050136 (p = 0.01). Stepwise multiple regression analysis suggested that, among 4 SNPs, rs9939609 was the strongest predictor of weight gain after 6 months of risperidone treatment (p = 0.001). CONCLUSIONS: The FTO gene polymorphisms, especially rs9939609, seem to be related to weight gain after risperidone treatment in Chinese Han patients with first episode schizophrenia.

Multiomics Analyses Reveal Microbiome-Gut-Brain Crosstalk Centered on Aberrant Gamma-Aminobutyric Acid and Tryptophan Metabolism in Drug-Naïve Patients with First-Episode Schizophrenia.

BACKGROUND AND HYPOTHESIS: Schizophrenia (SCZ) is associated with complex crosstalk between the gut microbiota and host metabolism, but the underlying mechanism remains elusive. Investigating the aberrant neurotransmitter processes reflected by alterations identified using multiomics analysis is valuable to fully explain the pathogenesis of SCZ. STUDY DESIGN: We conducted an integrative analysis of multiomics data, including the serum metabolome, fecal metagenome, single nucleotide polymorphism data, and neuroimaging data obtained from a cohort of 127 drug-naïve, first-episode SCZ patients and 92 healthy controls to characterize the microbiome-gut-brain axis in SCZ patients. We used pathway-based polygenic risk score (PRS) analyses to determine the biological pathways contributing to genetic risk and mediation effect analyses to determine the important neuroimaging features. Additionally, a random forest model was generated for effective SCZ diagnosis. STUDY RESULTS: We found that the altered metabolome and dysregulated microbiome were associated with neuroactive metabolites, including gamma-aminobutyric acid (GABA), tryptophan, and short-chain fatty acids. Further structural and functional magnetic resonance imaging analyses highlighted that gray matter volume and functional connectivity disturbances mediate the relationships between Ruminococcus_torgues and Collinsella_aerofaciens and symptom severity and the relationships between species Lactobacillus_ruminis and differential metabolites l-2,4-diaminobutyric acid and N-acetylserotonin and cognitive function. Moreover, analyses of the Polygenic Risk Score (PRS) support that alterations in GABA and tryptophan neurotransmitter pathways are associated with SCZ risk, and GABA might be a more dominant contributor. CONCLUSIONS: This study provides new insights into systematic relationships among genes, metabolism, and the gut microbiota that affect brain functional connectivity, thereby affecting SCZ pathogenesis.

No effect of adjunctive, repeated-dose intranasal insulin treatment on psychopathology and cognition in patients with schizophrenia.

OBJECTIVE: This study examined the effect of adjunctive intranasal insulin therapy on psychopathology and cognition in patients with schizophrenia. METHODS: Each subject had a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia or schizoaffective disorder and been on stable antipsychotics for at least 1 month. In an 8-week randomized, double-blind, placebo-controlled study, subjects received either intranasal insulin (40 IU 4 times per day) or placebo. Psychopathology was assessed using the Positive and Negative Syndrome Scale and the Scale for Assessment of Negative Symptoms. A neuropsychological battery was used to assess cognitive performance. The assessment for psychopathology and cognition was conducted at baseline, week 4, and week 8. RESULTS: A total of 45 subjects were enrolled in the study (21 in the insulin group and 24 in the placebo group). The mixed model analysis showed that there were no significant differences between the 2 groups at week 8 on various psychopathology and cognitive measures (P > 0.1). CONCLUSIONS: Adjunctive therapy with intranasal insulin did not seem to be beneficial in improving schizophrenia symptoms or cognition in the present study. The implications for future studies were discussed.

An exploratory study examining lipid-lowering medications in reducing fasting serum lipids in schizophrenia patients treated with atypical antipsychotics.

BACKGROUND: We present a retrospective study examining response to treatment with fibrates or statins in schizophrenia patients. METHODS: We identified the patient population using the Research Patient Data Registry. Demographic data, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and non-HDL cholesterol (non-HDL-C) levels were obtained before initiation of treatment with lipid-lowering medication (LLM) and after LLM treatment was initiated (N = 183). RESULTS: Treatment with LLMs resulted in a statistically significant decrease in total cholesterol, triglycerides, LDL-C, and non-HDL-C. An independent-samples t test comparing the statin treatment-alone group with the fibrate treatment-alone group showed a significant reduction in triglyceride levels from baseline to 1-year follow-up in the fibrate treatment-alone group. CONCLUSIONS: The results of this study indicate that schizophrenia patients respond to LLMs in a manner consistent with the general population. Future studies would benefit from a larger sample, as well as comparisons between more specific treatment groups, such as those defined by type of statin or fibrate, to observe differential effects on specific markers of dyslipidemia in this population.

Exploring Zentangle as a virtual mindfulness-based art intervention for people with serious mental illness.

Introduction: Zentangle is an emerging art intervention that incorporates mindfulness into creative drawing. This pilot study explored Zentangle as a novel adjunct treatment for people with serious mental illness (SMI). Methods: Six participants with SMI completed an 8-week Zentangle program. Psychiatric outcomes were evaluated using the Brief Psychiatric Rating Scale (BPRS), Mindful Attention Awareness Scale (MAAS), Perceived Stress Scale (PSS), and Quality of Life Enjoyment and Satisfaction Scale (Q-LES-Q-SF). A focus group was conducted to better understand the experiences of the participants. Results: A significant reduction in psychiatric symptoms was observed as measured by the total score on the BPRS between baseline and 5-week post-intervention (40.7 ± 9.1 vs. 33.7 ± 8.9, mean ± SD, p = 0.02). Participants also showed a significant increase in mindful attention using the average score on the MAAS between 1- and 5-week post-intervention (3.5 ± 0.4 vs. 4.2 ± 0.7, mean ± SD, p = 0.04). Four themes were generated from the focus group: (1) approaching mindfulness through Zentangle; (2) power of uncomplicated art creation; (3) understanding the value of self-appreciation; and (4) fostering a positive environment. Discussion: Our preliminary data suggest that the use of Zentangle for participants with SMI may have a positive impact on overall psychiatric symptoms and mindfulness. Moreover, the Zentangle Method encourages positive emotions like gratitude and self-accomplishment to counteract negative feelings of self-criticism and failure in participants.

The effect of serum lipids and short-chain fatty acids on cognitive functioning in drug-naïve, first episode schizophrenia patients.

OBJECTIVE: Many studies have reported the important role of serum levels of short-chain fatty acids (SCFAs) in lipid metabolism and cognitive dysfunction. This study investigated the role of plasma lipids and SCFAs on cognitive functioning in drug- naïve first episode schizophrenia. METHODS: This study recruited 44 schizophrenia inpatients and 35 healthy controls. Plasma lipid metabolism was characterized using standard enzymatic methods and an automated analyzer. Serum levels of SCFAs were measured by Gas chromatography mass spectrometry (GC-MS). Cognitive performance was evaluated by the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: The patient group showed significantly higher serum levels of total SCFAs, acetic acid, acetic acid/ propionic acid ratio, and poorer cognitive scores compared with the control group (p's < 0.05). Within the patient group, the lipid levels were positively associated with acetic acid/ propionic acid ratio (p's < 0.05). Furthermore, multiple regression analysis revealed that the interactions of LDL level × acetic acid/ propionic acid ratio was a significant predictor of the MCCB working memory, and processing speed subscale scores within the patient group. CONCLUSIONS: Cognitive dysfunction and abnormal serum levels of SCFAs occur in the early phase of schizophrenia. Lipid metabolism and serum levels of SCFAs might be, both independently or interactively, associated with cognitive dysfunction in schizophrenia.

The role of white matter abnormality in the left anterior corona radiata: In relation to formal thought disorder in patients with schizophrenia.

White matter abnormality has been widely reported in patients with schizophrenia (Sz). However, few studies have focused on the relationship between the white matter deficit and formal thought disorder (FTD). Moreover, the role of genetic high risk in FTD-related white matter deficit remains unclear. The present study recruited 46 Sz patients, 18 unaffected first-degree relatives of Sz patients, and 29 healthy controls. There was a widespread fractional anisotropy (FA) reduction in Sz. In addition, reduced FA in the left anterior corona radiata was related to more severe FTD symptoms in Sz. However, the genetic high-risk group only showed lower mean FA in the left anterior limb of the internal capsule than healthy controls. Our findings suggest that abnormality in the left anterior corona radiata may only occur in Sz but not in the genetic high-risk group. Such an abnormality might be associated with the severity of FTD symptoms. Meanwhile, genetic vulnerability may contribute to the abnormality in the left anterior limb of the internal capsule. Better analytical methods are needed to validate our results.

Gut mycobiota dysbiosis in drug-naïve, first-episode schizophrenia.

Bacterial dysbiosis has been demonstrated in patients with schizophrenia (SCH). The aim of the present study was to investigate alterations in mycobiota composition and fungi-bacteria correlation network in drug-naïve, first episode SCH. We recruited 205 SCH patients and 125 healthy controls (HCs), whose gut bacterial and fungal compositions were characterized by 16S and 18S ribosomal RNA gene amplicon sequencing, respectively. Fungal-bacterial relative correlation network analysis was performed using the Spearman's test and distance correlation. We also computed relative networks connectedness, which represents the ratio of significant interactions (edges) and taxa (nodes) in the network. SCH patients showed lower fungal α-diversity compared with that of HCs. Furthermore, we identified 29 differential fungal markers at multiple taxonomies between SCH patients and HCs. SCH patients also showed a significantly lower fungi-to-bacteria α-diversity ratio compared with that of HCs (p = 1.81 × 10-8). In risk prediction models, we observed that combining bacterial and fungal markers achieved higher accuracy than that of bacterial markers alone (AUC = 0.847 vs AUC = 0.739; p = 0.043). Fungal-bacterial correlation network was denser in HCs than in SCH patients and was characterized by a high number of neighbors (p < 0.05). In addition, an increased abundance of Purpureocillium was associated with more severe psychiatric symptoms and poorer cognitive function in SCH patients (p < 0.05). Our study demonstrated a disrupted and weakened fungi-bacteria network in SCH patients, which might be associated with their clinical manifestations. Future research on fungal-bacterial correlation network is warranted to advance our understanding about the role of mycobiota in the etiology of SCH and to explore novel intervention approaches.

No effect of single-dose intranasal insulin treatment on verbal memory and sustained attention in patients with schizophrenia.

BACKGROUND: Impairments in verbal memory and attention are among the most severe and disabling cognitive deficits in patients with schizophrenia. Whereas efficacy for cognition has not yet been established for any pharmacologic strategy in schizophrenia, an accumulating body of evidence suggests a possible beneficial role of insulin. METHODS: We conducted a double-blind, placebo-controlled trial to examine the effect of single-dose intranasal insulin treatment on cognition in nondiabetic patients with schizophrenia. After fasting for 12 hours, subjects received either 40 IU regular human insulin or placebo administered by intranasal pump. The Hopkins Verbal Learning Test and the Continuous Performance Test-Identical Pairs were administered before and 30 minutes after intranasal treatment. RESULTS: Thirty patients were enrolled and completed the study. The 2 treatment groups (insulin vs placebo, n = 15 in each group) did not differ on any demographic or general clinical variable (P > 0.40). There was no significant difference between the 2 treatment groups in change on Hopkins Verbal Learning Test immediate recall total score and delayed recall score, or on CPT d', hits rate, reaction time of hits, or false-alarm rate (P > 0.1). CONCLUSIONS: Results of the present study suggest that single-dose intranasal insulin treatment does not have a large-enough effect on verbal memory or sustained attention to be detected by a sample of this size in patients with schizophrenia but was safe and well tolerated. Longitudinal studies to explore cognitive benefits of repeated dosing of intranasal insulin treatment are needed.

Placebo-controlled pilot study of ramelteon for adiposity and lipids in patients with schizophrenia.

OBJECTIVE: Few interventions have been successful to prevent or reverse the medical complications associated with antipsychotic agents in the schizophrenia population. In particular, no single agent can correct multiple metabolic abnormalities such as insulin resistance, hyperlipidemia, inflammation, obesity, and fat distribution. We now report a randomized placebo-controlled pilot study to examine the effects of ramelteon on obesity and metabolic disturbances among subjects with schizophrenia. METHODS: A double-blind, placebo-controlled, 8-week pilot trial was conducted, adding ramelteon 8 mg/d to stable outpatients with schizophrenia. Vital signs and anthropometric measurements, including height, weight, waist circumference, and body fat were assessed, and laboratory assays were tracked to monitor changes in metabolic markers. RESULTS: Twenty-five subjects were randomly assigned to treatment with study drug or placebo, and 20 subjects were included in the final analysis. Ramelteon did not improve anthropometric measurements, glucose metabolism, and inflammatory markers. There was, however, a significant decrease in total cholesterol and ratio of cholesterol to high-density lipoprotein in the ramelteon group. Although the standard anthropometric measures did not show significant change, the dual-energy x-ray absorptiometry scan showed a trend toward reduction in fat in the abdominal and trunk areas with a moderate effect size. CONCLUSIONS: Although ramelteon decreased cholesterol, treatment may have to be longer than 8 weeks and with a higher dose for maximal effect of ramelteon for body fat and lipid changes. Future studies are needed for patients with schizophrenia with a larger sample size to fully understand ramelteon's effects on abdominal adiposity and lipids.

A narrative review of mindfulness-based therapy for schizophrenia, co-occurring substance use and comorbid cardiometabolic problems.

Mindfulness-based therapy (MBT) has gained attention in recent years as a promising treatment for patients with schizophrenia for whom traditional interventions are not effective. Research demonstrates improvements in psychotic symptoms, emotion regulation, and other areas including re-hospitalization rates and insight into illness following MBT interventions. Yet MBT studies have not carefully reported results in patients with schizophrenia and co-occurring substance use or comorbid medical problems, bringing into question the generalizability of these findings. This narrative review explores the literature regarding the use of mindfulness-based interventions for patients with schizophrenia as well as for patients with substance use disorder, cardiovascular disease, obesity, and diabetes. Findings suggest that MBTs can improve craving in substance use disorder, eating related behaviors in obesity, diabetes-related distress, and metabolic regulation in patients with diabetes. Increased insula and anterior cingulate cortex volumes and activities following MBTs might be associated with the potential benefit of MBTs in patients with schizophrenia. Our review provides a foundational basis in support of the need for future studies evaluating the safety and efficacy of MBTs for schizophrenia with co-occurring substance use disorder and/or comorbid cardiometabolic problems.